minnelide™ capsules alone and in combination with paclitaxel in advanced gastric cancer

Conditions: Gastric Cancer

Summary: a phase 1, open-label, dose-escalation, safety, pharmacokinetic and pharmacodynamic study of minnelide™ capsules given alone or in combination with paclitaxel in patients with advanced gastric cancer.

minnelide™ is a water soluble disodium salt variant of triptolide, a diterpenoid, an hsp70 inhibitor. studies using orthotopic pancreatic cancer cell lines and human xenograft transplants demonstrate that minnelide™ prevents tumor progression, increases survival, and causes tumor regression.

Eligibility criteria:
inclusion criteria: * patients with histologically confirmed advanced gastric cancer * tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy * one or more metastatic tumors measurable per recist v1.1 criteria * karnofsky performance ≥ 70% * life expectancy of at least 3 months * age ³ 19 years * signed, written irb-approved informed consent * a negative pregnancy test (if female) * acceptable liver function: * bilirubin 1.5 times upper limit of normal * ast (sgot), alt (sgpt) and alkaline phosphatase 2.5 times upper limit of normal (if liver metastases are present, then 5 x uln is allowed) * albumin ≥ 3.0 g/dl * acceptable renal function: o serum creatinine within normal limits, or calculated creatinine clearance ³ 60 ml/min/1.73 m2 for patients with creatinine levels above institutional normal. * acceptable hematologic status: * granulocyte * monotherapy: ³ 1,500 cells/mm3 * combination therapy with paclitaxel: ³ 2,000cells/mm3 platelet count ³ 100,000 (plt/mm3) * hemoglobin ³ 9 g/dl * urinalysis: o no clinically significant abnormalities * acceptable coagulation status: * pt ≤ 1.5 times institutional uln * ptt ≤ 1.5 times institutional uln * women of child- bearing potential and men must agree to use adequate contraception for men and women of child-producing potential, the use of effective contraceptive methods during the study and until 90 days after the last dose of ip for men or until 6 months after the last dose of ip for women or 6 months after the last dose of ip with paclitaxel for both men and women. exclusion criteria: new york heart association class iii or iv, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ecg * baseline qtc exceeding 470 msec (using the bazett's formula) and/or patients receiving class 1a or class iii antiarrhythmic agents. * active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. * pregnant or nursing women. note: for men and women of child-producing potential, the use of effective contraceptive methods during the study and until 90 days after the last dose of ip for men or until 6 months after the last dose of ip for women or 6 months after the last dose of ip with paclitaxel for both men and women. should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * treatment with radiation therapy (local therapy, non-target lesion, 2 weeks), major surgery, chemotherapy, biological agents or investigational therapy within 3 weeks prior to study treatment. * unwillingness or inability to comply with procedures required in this protocol * known infection with hiv, hepatitis b, or hepatitis c * serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor * patients who are currently receiving any other investigational agent * patients who are on a prohibited medication (section 4.3.2). * patients with biliary obstruction and/or biliary stent (regimen b only) * patients with a history of severe hypersensitivity reactions to products containing cremophor® el (eg, cyclosporin for injection concentrate and teniposide for injection concentrate). • patient with baseline anc\<1500/mm3

Keywords: gastric cancer